The primary structure of human apolipoprotein A-I has been determined, and a systematic analysis of the polymorphic forms of apoA-I performed. ApoA-I contains no carbohydrate, and the polymorphic forms of A-I do not appear to differ in primary or secondary structure. A single isosteric substitution has been observed in the sequence at position 71 where tyrosine replaces phenylalanine. Procedures have been developed for the isolation of plasma apolipoproteins by affinity chromatography. Antibodies have been prepared against the major apolipoproteins, and the antibodies coupled to sepharose. These procedures will markedly facilitate the isolation and characterization of the plasma apolipoproteins. New techniques for the automated sequence analysis of proteins and peptides have been developed utilizing a large reaction cup, and cold trap on a Beckman sequencer. With these techniques automated degradations can be extended and large proteins (greater than 250-350 residues) can now be analyzed with improved precision.